The incidence and severity of pertussis (whooping cough) have been controlled by widespread immunization of infants with inactivated Bordetella pertussis organisms (cellular vaccine or P component of DPT). These vaccines have limitations because they elicit high degree of local and systemic reactions and because they confer immunity for a limited duration of time and only in about 70 to 90% of the population. The identification of pertussis toxin, as a major, if not the sole protective antigen for B pertussis has led to the development of a toxoid derivative of this antigen for vaccine. Pertussis toxin was purified by affinity chromatography from the culture supernatant of B. pertussis and inactivated by a novel method with hydrogen peroxide under controlled conditions. The resulting product, called NICHD-PtXD, has less than 1% of its original binding and enzymatic activities and showed no pharmacologic properties of the holotoxin in in vivo assays such as histamine sensitization. Clinical evaluation in adults, then 18-month old children showed it to be safe and capable of inducing pertussis toxin neutralizing antibodies similar to those observed in children convalescent from disease. Clinical evaluation of NICHD-PtXD in infants used two immunization schedules: three, five and seven months, and three, five and twelve months (recommended schedule for Sweden). The vaccine showed no adverse reactions. In both groups of infants, high levels of antitoxin (neutralized in antibodies) were listed after the third injection. The antitoxin level in the group receiving the toxoid at three, five and twelve months was greater (p = 0.001) than infants injected at three, five and seven months. Clinical effectiveness studies in Sweden are underway. Covalent binding of pneumococcus-14, a polysaccharide type causing infant infections, to pertussis toxin both inactivated the toxin and induced both antitoxin and high levels of pneumococcus type 14 antibodies in mice.